Abstract Ensuring the success of conservation through protected areas relies on understanding whether management actions are successful or whether they need to be changed. Such management effectiveness evaluations are becoming increasingly common globally and are being used to adapt management actions and guide strategic planning and resource allocation within protected areas. Due to a lack of data about protected area management, generally evaluations are based on the knowledge of protected area managers. While this expert knowledge is a potentially plentiful and cost-effective option, it is important to consider the precision and accuracy of these data to understand the confidence that should be placed in this information before they are used to make significant changes to protected area management. However, this is the first study to examine the precision and accuracy of management effectiveness evaluations based on expert knowledge. To examine the confidence that can be placed in expert management effectiveness evaluation, this study focused on the State of the Parks evaluation tools, used by the Australian protected area management agencies Parks Victoria and the New South Wales Department of Conservation and Climate Change. Both the accuracy and precision of assessments are considered using a mixture of quantitative and qualitative methods. By establishing an independent reference point through on-ground data collection or a systematic review of existing data, the accuracy of park manager's assessments were evaluated. An analysis of the data sources available to park managers to support their assessments revealed that the majority of park managers did not use quantitative data. The accuracy of assessments was therefore measured for a sample of reserves where quantitative data were reportedly used and where practitioners had only experience to inform their assessments. The precision, or the consistency, of State of the Parks assessments was also examined. Two likely sources of inconsistency within State of the Parks data were considered: those arising from the use of language and those resulting from personal differences between managers. The magnitude of these errors was evaluated through a questionnaire and a series of interviews with park managers. These errors were then modelled to assess the factors that influence the error within assessments. This study demonstrates that over half of park managers accurately assess the conditions within their reserves with reference only on their personal management experience. This analysis also revealed that many park managers who report research and monitoring data as the basis of their assessments do not genuinely have data, thus artificially inflating the already low levels of quantitative data reported. A systematic review of the data available to support State of the Parks assessments revealed that even when data were genuinely available to managers these data were insufficient to support the assessment and so required interpretation of the basis of personal experience. This provides strong evidence that even quantitative assessments of management effectiveness are actually experience-based. Yet, experience is sufficient for accurate assessments in many cases. While many park managers can accurately asses the effectiveness of their management, inaccuracies appear to arise from inconsistency in how park managers interact with the State of the Parks assessment tool. Park managers were found to be inconsistent in how they interpreted the language used in assessments when terms were not clearly defined, introducing error into the data set. Likewise, where the answers to assessments could be framed in various ways, park managers varied in the scope, scale and timeframe considered for assessments. While these framing errors were common, they did not account for a significant error in the dataset, but are likely to vary between evaluation datasets collected in different years. Considering the combined effects of these errors in State of the Parks data (the total error), the most reliable assessments were made by park rangers with moderate amounts of experience and the managers of nature reserves if they had a tertiary level education. The results of this study should be viewed as a positive outcome for management effectiveness assessments based on expert knowledge. Over half of park managers made accurate assessments of their reserves and many of the inconsistencies recorded may be easily resolved through more careful elicitation of assessments. For example, the undefined terms used within the assessments currently cause park managers confusion, but using explicit management standards to eliminate personal interpretations should eliminate much of this bias. Likewise, where park managers frame with assessments of management differently, more explicit guidelines could ensure they understand what they should evaluate. These simple changes would result in higher levels of precision and more robust evaluation data sets, increasing the confidence with which they can be used to guide management. The findings of this research should encourage other management agencies to analyse the validity of their evaluation data sets and provide guidance for those wishing to develop similar assessment tools.


— In ambient and mobile learning contexts, 3D renderings create higher states of immersion compared to still images or video. To cope with the considerable effort to create 3D objects from images, with the NEMO Converter 3D (NOC3D) this paper presents a technical approach to automatically reconstruct 3D objects from semantically annotated media, such as photos and more importantly video footage, in a background process. By using the Mobile Learning Exploration System (MoLES) with a smartphone, the user creates and collects media in mobile context, which are automatically uploaded into the NEMO-Framework (Network Environment for Multimedia Objects) together with semantic annotations for contextualized access and retrieval. NEMO provides an extendable web-based framework to store media like photos, videos and 3D objects together with semantic annotations. The framework has been developed for Ambient Learning Spaces (ALS) in a research project. With InfoGrid, a mobile augmented reality application connected to NEMO, the user experiences the previously generated 3D object placed and aligned into real world scenes. 3D objects automatically reconstructed from photo and video footage by NOC3D are stored in NEMO and thus provided to all applications accessing the NEMO API. Related to the pedagogical background of our research project, this paper focuses on the technical realization and validation of NOC3D with reference to a realistic scenario for the usage of NOC3D in ambient and mobile contexts. In Section 2, we regard related work. In Section 3, we present a practical scenario for using NOC3D. In Sections 4, we describe the technical environment for NOC3D and our research project. In Section 5, we outline the realization of NOC3D in the ambient context of our scenario. In Section 6, we present our findings and conclude with a summary and outlook in Section 7.


This paper describes the prosodic phenomenon of reset inclination extending over a long stretch of expressive speech in French radio press reviews. The stretch of speech delimits a thematic sequence and covers different types of reported speech units, ranging from a single clause to several utterances. Within a number of those thematic sequences, an intonational parallelism occurs. At every repetition, a reset takes place at a higher level: this makes up an inclination of the fundamental frequency for the repeated segment throughout the thematic sequence. The argument is that reset inclination constitutes a marker that has three effects: from a syntactic point of view it co-occurs with an enumeration effect; considered as an iconic representation, it is a rise because of an upward slope movement; from a pragmatic point of view it signals the speaker's involvement and contextualises speech events. In some cases, reset inclination is also related to the superposition of voices in speech. This study aims at clarifying our understanding of the communicative function of organisational patterns in speech.


This paper focused on the analysis of the interpretation potential given by fluvial archives, in order to decipher the Mid- to Late Holocene sedimentary history. The database discussed here refers to 65 dated ages (mostly radiocarbon), mappings of the most representative floodplain reaches of Suceava, Moldova and Siret rivers, and 23 outcrops analysed in floodplain deposits (river banks or gravel pits). The study results concentrated on (a) describing the regional features of Eastern Carpathian floodplains, (b) the floodplain morphology and its correlation with the structure of fluvial deposits and (c) identifying the paleoevents of fluvial activity on a centennial timescale. In this way, we were able to identify a general pattern of the dynamic geomorphology history for the rivers situated eastward of the Carpathians, which resulted from combining the Mid- to Late Holocene sedimentation phases, the avulsion and lateral migration processes that occurred during high fluvial activity intervals and the morphological adjustment of the rivers channels, from braiding to wandering and sinuously–meandering. The chronological overlay of the events revealed that the time intervals with the most extensive fluvial processes on the rivers draining the Eastern Carpathians occurred (in years before present) during 6200, 5300, 4100–4080, 3600, 2300–2200 (Iron Age), 1300 (Migrations Period), 950–970 (Medieval Climate Anomaly), 750–520 BP (Little Ice Age)and that these intervals generally overlap the high precipitation palaeoclimatic episodes documented in Romania. The fluvial activity of the rivers during the Mid- to Late Holocene has been compared as well with several records of paleo–climates variability over the geographical area of Romania. The result showed that many flooding episodes were coincident with the wet and cold intervals which were also identified in the variation of the other proxydata, especially after 4.7 kcal BP.


Prepared in conjunction with the 2012 GSA Cordilleran Section Meeting, Queretaro, Mexico, this volume's eight field guides showcase three aspects of the geology of the southern end of the North America cordillera: Mid-Tertiary and Quaternary volcanology, environmental geology, and Mesozoic tectonics. Field Guide 25 explores the Cenozoic stratigraphy of Sierra de Guanajuato, one of the most important Mexican mining districts, and addresses a controversial topic, the accretion of the Guerrero terrane and its possible role in the Late Cretaceous—Early Tertiary orogeny. Three guides related to the Trans-Mexican Volcanic Belt, an active magmatic arc related to subduction of the Rivera and Cocos plates, include new data about the recent volcanic history, physical volcanology, and volcanic hazards in Mexico's most densely populated area. Bringing the geosciences into societal problems, one guide presents data on ground deformation related to water extraction in urbanized areas of the Mexico City basin, and another explores the ghost town of the Mineral de Pozos mining district and the effect of mine tailings on groundwater.


Family planning and other health care organizations in developing countries increasingly must do more with the same resources and sometimes with fewer. Reorganizing work processes offers one common-sense way to help staff members at all levels cope with growing demands. Whether you are a clinic manager front-line provider program supervisor or district-level manager you can improve how work is organized and performed. Often simple changes enable organizations to serve clients better offer more satisfying work to the staff operate more effectively cut waste and even reduce or recover costs. (excerpt)


The purpose of this study is to examine the relationship between perceptions held by accountants regarding the e-service quality dimensions of the e-government website in connection with their behavioral and praising intentions. Using the survey method, 203 responses were collected from accountants in Turkey. A partial least square structural equation model was constructed to test both the reliability and validity of the measurement as well as the structural model. The results showed that several e-service quality sub-dimensions such as graphical quality, emotional benefits, and ease of use and control have a positive and significant impact on behavioral intention and praising intention. The study did not find support for the possible effect of layout clarity upon behavioral intention and praising intention.


Living in a new country is a contemporary condition. We are all migrants even if we stay at home. But migration is not only a cultural and historical fact - it also represents a poetic attitude, a willingness to improvise new cultural forms. In this collection of essays, Paul Carter moves from European ways of travelling Australia to the elaboration of a contemporary performance practice, to show how our deeply-ingrained tendency to visualize knowledge has led us to ignore the historically important, but invisible, dimensions of speech and sound. Revealing what he describes as the "dialogical space", opened up whenever different cultures come into contact and attempt to speak to one another, the author shows how a more perceptually-attuned history can lead to a "migrant aesthetic" both environmentally friendly and spiritually liberating.


Stroke is a multifactorial disease that may be associated with aberrant DNA methylation profiles. We investigated epigenetic dysregulation for the methylenetetrahydrofolate reductase (MTHFR) gene among ischemic stroke patients. Cases and controls were recruited after obtaining signed written informed consents following a screening process against the inclusion/exclusion criteria. Serum vitamin profiles (folate, vitamin B12, and homocysteine) were determined using immunoassays. Methylation profiles for CpGs A and B in the MTHFR gene were determined using a bisulfite-pyrosequencing method. Methylation of MTHFR significantly increased the susceptibility risk for ischemic stroke. In particular, CpG A outperformed CpG B in mediating serum folate and vitamin B12 levels to increase ischemic stroke susceptibility risks by 4.73-fold. However, both CpGs A and B were not associated with serum homocysteine levels or ischemic stroke severity. CpG A is a potential epigenetic marker in mediating serum folate and vitamin B12 to contribute to ischemic stroke.


: H-2b lymphocytes were sensitized against H-2d alloantigens by lymphocyte culture reaction and incubated with H-2d mastocytoma cells. The interaction between lymphoid cells and mastocytoma cells was stopped by fixation with glutaraldehyde. The areal density of the cytoplasmic vacuoles as well as the subcellular localization of acid phosphatase in lymphocytes were examined by electron microscopy. Two populations of lymphocytes were observed, small lymphocytes with heterochromatic nuclei and larger lymphocytes (lymphoblasts) with euchromatic nuclei. Only the lymphoblasts showed change following interaction with target cells. The vacuole area in percent of cytoplasmic area (vacuole areal density) of sensitized lymphoblasts increased during the first 30 minutes and from the third to fourth hour of interaction with target cells. Acid phosphatase staining was observed in the Golgi apparatus of the lymphoblasts after 30 minutes of interaction. Multivesicular bodies showed acid phosphatase staining within 20 minutes of interaction with target cells. After 20 minutes of interaction, phagosomes containing myelin figures were formed. These phagosomes also showed acid phosphatase staining and during the next hours of interaction their number increased over the number of multivesicular bodies.


Hepatitis C virus (HCV) infection is a major public health problem in the European Union (EU). An estimated 5.6 million Europeans are chronically infected with a wide range of variation in prevalence across European Union countries. Although HCV continues to spread as a largely "silent pandemic," its elimination is made possible through the availability of the new antiviral drugs and the implementation of prevention practices. On 17 February 2016, the Hepatitis B & C Public Policy Association held the first EU HCV Policy Summit in Brussels. This summit was an historic event as it was the first high‐level conference focusing on the elimination of HCV at the European Union level. The meeting brought together the main stakeholders in the field of HCV: clinicians, patient advocacy groups, representatives of key institutions and regional bodies from across European Union; it served as a platform for one of the most significant disease elimination campaigns in Europe and culminated in the presentation of the HCV Elimination Manifesto, calling for the elimination of HCV in Europe by 2030. The launch of the Elimination Manifesto provides a starting point for action in order to make HCV and its elimination in Europe an explicit public health priority, to ensure that patients, civil society groups and other relevant stakeholders will be directly involved in developing and implementing HCV elimination strategies, to pay particular attention to the links between hepatitis C and social marginalization and to introduce a European Hepatitis Awareness Week.


We present the PICTOR browser, a visualization designed to facilitate the analysis of quotations about userspecified topics in large collections of news text. PICTOR focuses on quotations because they are a major vehicle of communication in the news genre. It extracts quotes from articles that match a user's text query, and groups these quotes into "threads" that illustrate the development of subtopics over time. It allows users to rapidly explore the space of relevant quotes by viewing their content and speakers, to examine the contexts in which quotes appear, and to tune how threads are constructed. We offer two case studies demonstrating how PICTOR can support a richer understanding of news events.


Abdominal aortic aneurysm is associated with infiltration of inflammatory cells into the aortic wall. The inflammatory response is also evident in animal models, such as apolipoprotein E-deficient (ApoE-/-) mice that have been infused with angiotensin II, prior to development of aortic aneurysm. Since omega-3 polyunsaturated fatty acids (n-3 PUFAs) and their metabolites have anti-inflammatory and pro-resolving activity, we hypothesised that dietary supplementation with n-3 PUFAs would protect against inflammatory processes in this mouse model. Twenty C57 and 20 ApoE-/- 3-4 week old male mice were supplemented with a low (0.14%, n = 10/group) or high (0.70%, n = 10/group) n-3 PUFA diet for 8 weeks before 2-day infusion with 0.9% saline or angiotensin II (1000 ng/kg/min). Four ApoE-/- mice on the low n-3 PUFA diet and none of the ApoE-/- mice on the high n-3 PUFA diet showed morphological evidence of abdominal aortic dissection. The plasma concentration of the n-3 PUFA metabolite, resolvin D1 was higher in angiotensin II-infused ApoE-/- mice fed the high, compared to the low n-3 PUFA diet. The number of neutrophils and macrophages infiltrating the abdominal aorta was elevated in ApoE-/- mice on the low n-3 PUFA diet, and this was significantly attenuated in mice that were fed the high n-3 PUFA diet. Most neutrophils and macrophages were associated with dissected aortas. Immunoreactivity of the catalytic subunit of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, Nox2, and superoxide were elevated in ApoE-/- mice that were fed the low n-3 PUFA diet, and this was also significantly attenuated in mice that were fed the high n-3 PUFA diet. Together, the findings indicate that supplementation of ApoE-/- mice with a diet high in n-3 PUFA content protected the mice against pro-inflammatory and oxidative stress responses following short-term infusion with angiotensin II.


Porous graphene has a high mechanical strength and an atomic-layer thickness that makes it a promising material for material separation and biomolecule sensing. Electrostatic interactions between charges in aqueous solutions are a type of strong long-range interaction that may greatly influence fluid transport through nanopores. In this study, molecular dynamic simulations were conducted to investigate ion and water transport through 1.05-nm diameter monolayer graphene nanopores, with their edges charge-modified. Our results indicated that these nanopores are selective to counterions when they are charged. As the charge amount increases, the total ionic currents show an increase–decrease profile while the co-ion currents monotonically decrease. The co-ion rejection can reach 76.5% and 90.2% when the nanopores are negatively and positively charged, respectively. The Cl– ion current increases and reaches a plateau, and the Na+ current decreases as the charge amount increases in systems in which Na+ ions act as counterions. In addition, charge modification can enhance water transport through nanopores. This is mainly due to the ion selectivity of the nanopores. Notably, positive charges on the pore edges facilitate water transport much more strongly than negative charges.


Introduction Peroxiredoxins are a family of highly conserved antioxidant proteins. Beside its role in the reduction of peroxides, Peroxiredoxin-4 (Prdx4) has been shown to play a role in the modulation of pro-inflammatory signalling cascades. Our group has previously demonstrated that Prdx4 is expressed in the intestinal mucosa and upregulated upon stimulation with the bacterial cell wall component muramyl-dipeptide (MDP). In addition, siRNA-mediated downregulation of Prdx4 increased MDP-induced NF-κB signalling. We therefore generated a murine Prdx4-knockout model to address the relevance of Prdx4 in the intestinal immune response in vivo . Methods In this study, two different Prdx4-knockout mouse lines were used: A constitutive Prdx4‑/- knockout strain, in which global Prdx4 expression was deleted and a conditional mouse line that specifically lacked Prdx4 in the intestinal epithelium (Prdx4 ΔIEC/ΔIEC). Intestinal inflammation was induced by administration of dextran-sodium-sulfate (DSS) in the drinking water of Prdx4 -/-, Prdx4 ΔIEC/ΔIEC and respective littermate control mice. Mice were assessed for weight loss, disease severity, histopathology and endoscopic appearance. Results We found that during DSS-induced colitis Prdx4 -/- mice lost significantly more weight and had a more pronounced disease activity than their wild-type littermates. However, no such differences were observed in Prdx4 ΔIEC/ΔIEC mice, compared to their Prdx4 floxed/floxed littermates. Likewise, colon histopathology and endoscopy did not reveal significant differences. We next examined Prdx4 expression in dissociated intestinal segments and found that Prdx4 levels in the lamina propria exceeded those of the intestinal epithelium (foldchange >2). In addition, already under basal conditions, lamina propria immune cell composition differed significantly between Prdx4 -/- and wild-type mice. Conclusion Our data assign a protective role of Peroxiredoxin-4 in intestinal inflammation which does not arise from the intestinal epithelium but presumably from the lamina propria. Further studies will be needed to determine the functional basis and molecular mechanisms of the observed effects. Disclosure of Interest None Declared.


ES cells can propagate indefinitely, maintain self-renewal, and differentiate into almost any cell type of the body. These properties make them valuable in the research of embryonic development, regenerative medicine, and organ transplantation. MicroRNAs (miRNAs) are considered to have essential functions in the maintenance and differentiation of embryonic stem cells (ES cells). It was reported that, strong external stimuli, such as a transient low-pH and hypoxia stress, were conducive to the formation of induced pluripotent stem cells (iPS cells). AICA ribonucleotide (AICAR) is an AMP-activated protein kinase activator, which can let cells in the state of energy stress. We have demonstrated that AICAR can maintain the pluripotency of J1 mouse ES cells through modulating protein expression in our previous research, but its effects on ES cell miRNA expression remain unknown. In this study, we conducted small RNA high-throughput sequencing to investigate AICAR influence on J1 mouse ES cells by comparing the miRNA expression patterns of the AICAR-treated cells and those without treatment. The result showed that AICAR can significantly modulate the expression of multiple miRNAs, including those have crucial functions in ES cell development. Some differentially expressed miRNAs were selected and confirmed by real-time PCR. For the differently expressed miRNAs identified, further study was conducted regarding the pluripotency and differentiation associated miRNAs with their targets. Moreover, miR-134 was significantly down-regulated after AICAR treatment, and this was suggested to be directly associated with the up-regulated pluripotency markers, Nanog and Sox2. Lastly, Myc was significantly down-regulated after AICAR treatment; therefore, we predicted miRNAs that may target Myc and identified that AICAR induced up-regulation of miR-34a, 34b, and 34c can repress Myc expression in J1 mouse ES cells. Taken together, our study provide a new mechanism for AICAR in ES cells pluripotency maintenance and give insight for its usage in iPS cells generation.


With the coming into force of the Lisbon Treaty, EU law now contains explicit references to minority rights in Article 2 TEU and Article 21 of the Charter of Fundamental Rights. Combined with other EU norms on non-discrimination on the grounds of race or ethnic origin, and policies on culture and education, these references may be regarded as providing the preconditions for an EU regime of minority protection. This thesis investigates whether the EU should take these developments any further, and play more prominent role in protecting minorities in its Member States. This research question is addressed through four case studies on various aspects of minority protection, i.e., (1) the right to political participation, (2) the freedom to manifest religion, (3) the right to mother-tongue education, and (4) the right to autonomy. The case studies, based on examples from EU Member States (namely Latvia, Belgium and the United Kingdom), highlight that the EU could undoubtedly play a greater role in minority protection. However, instead of enacting its own rules on their protection, a more practical way forward could be for the EU to support implementation of the Council of Europe's Framework Convention for the Protection of National Minorities by Member States.


Cognitive linguistics scholars argue that metaphor is fundamentally a conceptual process of mapping one domain of experience onto another domain. The study of metaphor in the context of Translation Studies has not, unfortunately, kept pace with the discoveries about the nature and role of metaphor in the cognitive sciences. This study aims primarily to fill part of this gap of knowledge. Specifically, the thesis is an attempt to explore some implications of the conceptual theory of metaphor for translation. Because the study of metaphor in translation is also based on views about the nature of translation, the thesis first presents a general overview of the discipline of Translation Studies, describing the major models of translation. The study (in Chapter Two) then discusses the major traditional theories of metaphor (comparison, substitution and interaction theories) and shows how the ideas of those theories were adopted in specific translation studies of metaphor. After that, the study presents a detailed account of the conceptual theory of metaphor and some hypothetical implications for the study of metaphor in translation from the perspective of cognitive linguistics. The data and methodology are presented in Chapter Four. A novel classification of conceptual metaphor is presented which distinguishes between different source domains of conceptual metaphors: physical, human-life and intertextual. It is suggested that each source domain places different demands on translators. The major sources of the data for this study are (1) the translations done by the Foreign Broadcasting Information Service (FBIS), which is a translation service of the Central Intelligence Agency (CIA) in the United Sates of America, of a number of speeches by the Iraqi president Saddam Hussein during the Gulf Crisis (1990-1991) and (2) official (governmental) Omani translations of National Day speeches of Sultan Qaboos bin Said of Oman.


Lactating New Zealand fur seals Arctocephalus forsteri utilise 2 ecological regions: con- tinental shelf habitats and oceanic habitats associated with the Subtropical Front. Using milk fatty acids (FA) obtained from 29 satellite-tracked fur seals, we characterised the FA composition of seals that foraged on the continental shelf, and those that foraged in oceanic waters. Seals that foraged within oceanic waters were characterised by milk being comparatively high in monounsaturated fatty acids (MUFA; 47.4 ± 4.4%, mean ± SD), and lower in polyunsaturated fatty acids (PUFA; 23.8 ± 4.0%) when compared to seals that foraged in continental shelf waters (MUFA 36.7 ± 5.4 and PUFA 31.4 ± 5.5%). Based on FA compositions, we predicted the likelihood that milk samples collected at random (n = 131) represented individual seals having foraged either on the continental shelf or in dis- tant oceanic waters. Results indicated that 74% (n = 97) of seals were likely to have foraged in oceanic waters, with 26% (n = 34) likely to have foraged within continental shelf waters. These results were supported by the small sub-sample of 29 satellite-tracked seals, which indicated that 62% of seals had foraged in oceanic waters. FA analysis and satellite-tracking results contrasted with scat analyses, from which only 7% of scats contained prey remains from oceanic waters. The results suggest scats were biased toward females foraging on the continental shelf. To further understand the diet of New Zealand fur seals, additional information on potential prey species that inhabit waters associated with the Subtropical Front south of Australia is required, as well as the continued devel- opment and application of alternative dietary techniques.


The HIV epidemic is an ongoing global health challenge. Prevention strategies are one means to combat HIV. Part of prevention incudes behavior modifications, circumcision, vaccine product development and oral and topical pre-exposure prophylaxis (PrEP). Topical PrEP products, also referred to as topical microbicides, are designed for vaginal or rectal application for the purpose of prevention of HIV-1 sexual transmission. Products being designed are coitally or pericoitally dependent or provide sustained release of the active agent for long term protection. The potency of antiretrovirals (ARVs) in HIV therapy promoted the exploration of their use as topical microbicides. Dapivirine (DPV) and Tenofovir (TFV) are replication inhibitors which have been explored as topical microbicides most widely in clinical trials. A 1% TFV vaginal gel applied in a coitally dependent fashion was shown to reduce HIV acquisition by 39%. However, other trials have not been able to show similar successful results with use of the same TFV gel. Therefore, to improve efficacy, combinations of ARVs are being pursued as topical microbicides. The development and characterization of a polymeric vaginal film containing DPV and TFV is presented in this dissertation. Drug – drug compatibility and a solid state solubility for polymer selection process are described. Physical and chemical characterization of the film demonstrated acceptable film properties. Efficacy testing in vitro showed the film to be effective at preventing HIV infection. Finally, stability testing proved the film to be stable at different environmental conditions for 6 months. Moreover, as ARVs drug tissue level is important for their bioactivity, the impact of the co-delivery of TFV and DPV on their tissue accumulation and distribution was assessed in an excised human ecto-cervical model. Results showed that the film was able to release both agents from the film for subsequent delivery into the target tissue. Interestingly, the data showed that the combination film product resulted in achieving higher DPV tissue amounts in the stroma whereas no impact on TFV tissue accumulation was observed. Collectively, these results provide evidence of the ability of polymeric films to accommodate ARVs combinations and illustrate the impact of co-delivery on drug tissue accumulation and distribution.


Just as the Petri dish has been invaluable to the evolution of biomedical science in the last 100 years, microfluidic cell assay platforms have the potential to change significantly the way modern biology and clinical science are performed. However, an evolutionary process of creating an efficient microfluidic array for many different bioassays is necessary. Specifically for a complete view of a cell response it is essential to incorporate cytotoxic, protein and gene analysis on a single system. Here we present a novel cellular and molecular analysis platform, which allows access to gene expression, protein immunoassay, and cytotoxicity information in parallel. It is realized by an integrated microfluidic array plate (iMAP). The iMAP enables sample processing of cells, perfusion based cell culture, effective perturbation of biologic molecules or drugs, and simultaneous, real-time optical analysis for different bioassays. The key features of the iMAP design are the interface of on-board gravity driven flow, the open access input fluid exchange and the highly efficient sedimentation based cell capture mechanism (∼100% capture rates). The operation of the device is straightforward (tube and pump free) and capable of handling dilute samples (5-cells per experiment), low reagent volumes (50 nL per reaction), and performing single cell protein and gene expression measurements. We believe that the unique low cell number and triple analysis capabilities of the iMAP platform can enable novel dynamic studies of scarce cells.


Linear autoregressive (LAR) models poorly predict asset prices in nonlinear, regime-switching markets. In this article, the authors use SETAR, a threshold model that accounts for nonlinearities, to test for the existence of regime-switching in global equity markets. A comparison of SETAR's predictive power against that of LAR models suggests that SETAR yields more accurate long forecasts, in both emerging and developed stock markets. The authors discuss extensions of threshold models into portfolio management, corporate valuation, and the long-term forecasting of financial indicators.


Current medical needs dictate that laboratories offer thyrotropin (TSH) assays that can reliably measure low TSH concentrations--a prerequisite for using the more cost-effective TSH-centered strategy currently recommended by the American Thyroid Association. This study reviews the functional performance of the TSH immunometric assay methods currently used in clinical practice. Methodological differences between methods, the rationale for using the 20% interassay CV as the functional sensitivity limit for patient reports, and both TSH-related and non-TSH-related specificity problems are reviewed. We recommend that manufacturers and clinical laboratories use a clinically relevant standard protocol for functional sensitivity assessments. In this protocol, human serum pools are analyzed in random order 10 or more times across a clinically realistic time span (which approximates to 6-8 weeks for TSH measurements used in an outpatient setting). Laboratories should independently establish and periodically check their functional sensitivity by the standard protocol and enlist the manufacturer's help to accomplish this if necessary. Manufacturers should (a) develop promotional material that realistically projects the assay's functional sensitivity expected in a clinical laboratory setting, (b) ensure that new clinical laboratory users achieve the projected functional sensitivity target when using the standard protocol, and (c) focus on the typical functional sensitivity obtained by clinical laboratory users rather than the assay's "generation" achieved under ideal conditions. If manufacturers and laboratories collaborate to solve the sensitivity and specificity problems discussed here, clinical laboratories should be better able to consistently deliver reliable serum TSH measurements across the full range of TSH concentrations encountered in clinical practice.


Abstract. The main aim of this study are the bacteria that most often cause clinical mastitis (CM) and their impact on milk reduction in Holstein-Friesian cows in the Pelagonia – North Macedonia region. 36 milk samples were taken from Holstein-Friesian breed of cows with confirmed clinical mastitis by a veterinarian. The samples were taken for the period from January 2019 to December 2020 from 20 different smallholder farms situated in the monitored region. Two sterile tubes with 10 ml of milk in each of them were taken from the affected part of the udder of the cow. A total of 86 tubes with milk from 36 mastitis cows were taken. From each sample 300 µl drips were placed in petri dishes with different selective nutrient media: Mannitol Salt Agar, MacConkey Agar, Endo Agar and Edwards nutrient medium. The petri dishes were incubated at 35±2°C for 24-48 hours in Mannitol Salt Agar, at 30-35°C for 18 to 72 hours in MacConkey Agar, at 35±2°C for 18 to 24 hours in Endo Agar and at 35-37°C for 24-48 hours in Edwards nutrient medium. Morphology of colonies and cells were examined with a microscope. A total of 119 strains were obtained and the following physiological and biochemical studies were performed to determine the new isolates: oxidase reaction, catalysis activity, indol test, hydrolysis of the hyporate, acetoin formation (acetylmethylcarbinol, Voges-Proscauer reaction) and Methyl-Roth test (MR- test). The results obtained revealed that the most common bacterial species causing clinical mastitis in Holstein-Friesian cows in 2019 and 2020 were six species of bacteria, where E. coli and Staphylococcus spp. are dominant.


For normal cochlear function, outer hair cells (OHCs) require a precise regulation of intracellular Ca2+ levels. Influx of Ca2+ occurs both at the stereocillia tips and through the basolateral membrane. In this latter compartment, two different origins for Ca2+ influx have been poorly explored: voltage-gated Ca2+ channels (VGCC) at synapses with type II afferent neurons, and α9α10 cholinergic nicotinic receptors at synapses with medio-olivochlear complex (MOC) neurons. Using functional imaging in rodent OHCs, we report that these two Ca2+ entry sites are closely positioned, but present different regulation mechanisms. Ca2+ spread from MOC synapses is contained by cisternal Ca2+-ATPases. Considered a weak drive for transmitter release, we unexpectedly found that VGCC Ca2+ signals are comparable in size to those elicited by α9α10 and can be potentiated by ryanodine receptors. Finally, we showed that sorcin, a highly expressed gene product in OHCs with reported Ca2+ control function in cardiomy-ocytes, regulates basal Ca2+ levels and MOC synaptic activity in OHCs.


In this work we investigate how the intrinsic spatial resolution varies with the number of digitized readout channels for a 64 (88) channel detector using a statistics-based positioning algorithm. We report results for both 6 mm and 8 mm thick crystals. Three channel reduction schemes are explored. The simplest scheme is row and column summing (R-C sum) of the photomultiplier tube channels. The second method is to only use channels with signals above a 1% threshold of the total signal (1% thres). The third method is to acquire a subset of PMT channels determined by the maximum signal channel (zone mask). The full width at half maximum (FWHM) intrinsic spatial resolution results for the central and corner sections of the detector are presented for each of the methods. All methods except R-C sum performed well for the central section of the detector. The 1% thres and zone mask schemes showed significant improvement for the corner section of the 6 mm thick crystal. All methods using a single depth look-up table had difficulty in the corner region for the 8 mm thick crystal. We believe this is caused by depth dependent edge effects on the light response function. Initial results using a depth dependent look-up table show improved positioning performance.


The geographical position of a territory is a statically element strictly determined by mathematical landmarks and by those of the natural background. For all that, different historical and geopolitical events that happened in the course of time, can make the geographical position fluctuate by including a territory / state into territorial aggregates established on less arbitrary criteria. Thus, many interwar authors placed Romania, by geographical criteria, in Central Europe; after 1945 they would include it in Eastern Europe, or in short, in the East, a political-ideological homogeneous territory, but heterogeneous geographically, historically and cultural. With the downfall of political-ideological barriers and the deep-going mutations in the geopolitics of Central and Eastern Europe, Romania's geographical position should be reconsidered based on objective criteria: geographical, mathematical and last but not least, cultural and economic. This study is also important because some recent works place Romania erroneously in South-Eastern Europe, either in Eastern or in Balkan Europe. The work concludes that Romania in a state situated in the south-eastern part of Central Europe. The arguments brought in favour of it have in view to push forward the current stage of knowledge on Romania's geopolitics.


In this study, a porous chitosan (CS)-organically modified montmorillonite (OM)-hydroxyapatite (HA) composite was developed by combining microwave irradiation and gas foaming method. The prepared composite was characterized using X-ray diffraction (XRD), attenuated total reflectance-fourier transform infrared (ATR-FTIR) spectroscopy, and scanning electron microscopy (SEM). The synergistic effect of OM and HA on the mechanical and in vitro biological properties (swelling, degradation and protein adsorption) of the composite were evaluated. In addition, the in vitro bioactivity of the composites was studied in simulated body fluid (SBF) for 21 days. The XRD results revealed the formation of an exfoliated structure upon incorporation of OM. ATR-FTIR studies indicated strong molecular interaction among the three different components of the composite. The CS-OM-HA composites exhibited a reduction in swelling, degradation and protein adsorption; whereas an enhancement in bioactivity was witnessed as evidenced by SEM analysis. Furthermore, the CS-OM-HA composites showed a significant enhancement in mechanical (tensile) property in comparison with pure chitosan (CS) and CS-OM composites. An in vitro cytotoxic assay was also performed to determine the biocompatibility of the prepared CS based composites. The results showed that the prepared CS based composites were non-toxic. From the study, it can be concluded that the novel CS-OM-HA composite with improved in vitro biological and mechanical properties has wide potential in non-load bearing orthopedic applications.


Although McClellan was the founder of a medical school and professor of surgery, his legacy of written material is pitifully small. Gross observed, "His reputation as a surgeon will be in great measure traditional, for he has left no adequate record of his observations and experience". Through notes such as these, we may develop a picture of the state of medical knowledge, the way in which it was taught and perhaps make inferences about the clinical expertise of Doctor McClellan.


The story has become all too familiar. Someone dies, and her loved ones request the contents of her text, email, or social media accounts. Perhaps they wish to preserve this vibrant electronic slice of the decedent's life. Perhaps they are compelled in their grieving to sift through the minutiae of the decedent's final days. Or perhaps they are merely trying to fulfill their duty as trustee, executor, or administrator to pay the decedent's bills and inventory her property. However, the decedent's Internet Service Provider ("ISP") — be it Facebook, Yahoo!, or Microsoft — refuses to comply. As Naomi Cahn explains in her outstanding contribution to the Vanderbilt Law Review's Symposium on the Role of Federal Law in Private Wealth Transfer, these ISPs are afraid of a byzantine federal statute from 1986: the Stored Communications Act ("SCA"). Section 2701 of the SCA criminalizes unauthorized access to electronic communications: a seemingly nasty glitch for fiduciaries attempting to marshal a decedent's digital assets. Section 2702 bars ISPs from disclosing a customer's private data without her "lawful consent." Citing the fact that the SCA predates the rise of email — let alone the phenomenon of a valuable Twitter account — Professor Cahn argues that the statute should not govern fiduciaries. Alternatively, assuming that the SCA does apply, Professor Cahn discusses various ways around this obstacle, including the Uniform Law Commission's draft Fiduciary Access to Digital Assets Act ("FADA"), which would clarify that fiduciaries generally enjoy the "authorization"' and "lawful consent" necessary to acquire a decedent's online accounts. This short invited reply takes a different route to the same destination. It begins by offering a reading of the SCA that diverges slightly from Professor Cahn's. However, it uses that discussion to echo her critique of the SCA and bolster the case for the FADA.


Objective: Moisture damage in buildings is a common problem. Prolonged exposure to dampness microbiota is a health hazard. There is convincing evidence of increased risk of new asthma or asthma exacerbation due to exposure to dampness microbiota and to decaying products in building materials. In addition, irritation symptoms such as rhinitis, cough, eye problems, eczema, headache, and fatigue have been reported. Certain other diseases might also be associated with exposure to dampness microbiota.
Design: Here, we describe four cases of individuals working in water-damaged buildings who in addition to respiratory diseases, suffered from tendinitis, synovitis, arthralgias, muscular pain, cardiac arrhythmias, and urticaria.
Conclusion: We review the contemporary literature and present arguments that prolonged or cumulative exposure to dampness microbiota may cause far more complicated disease than asthma alone.


Humor has been positively perceived in general. However, research has shown that a leader should adopt humor with care and only after considering the relevant context, such as cultural differences. This study was undertaken to gain insight into how leader humor is perceived in the predominantly Confucian culture of Taiwan, through a series of in-depth interviews with individuals from throughout the hierarchies of various organizations. Overall, our participants expressed conflicting attitudes toward leader humor in the workplace, depending on the place and time of their leader humor experience. Specifically, leader humor was deemed more effective in informal domains and when a good leader–follower relationship exists. The findings echo the implicit theory of leadership and highlight the need to consider the context when exercising leader humor in Confucian cultures. Implications and future study directions are discussed.


This paper presents theory and simulation of flowinduced structures, useful to the creation of synthetic material structures and to the biomimetics of natural fibers. We present a multiscale theory and simulation of hydrodynamic texture formation to provide fundamental principles for control and optimization of structures in liquid crystal polymers. In thermotropic flow-aligning nematic polymers it found that as the shear-rate increases, the pathway between an oriented non-planar state and an oriented planar state is through texture formation and coarsening, temperature and shear rate being efficient fields to control the grain size of the texture. High temperatures and shear rates lead to defect free monodomains. The texture transition cascade: unoriented monodomain defect lattice defect gas oriented monodomain is remarkably consistent with the experimentally observed textural transitions of sheared lyotropic nematic polymers.


The growing complexity of today's system designs requires fast and robust verification methods. Existing BDD, SAT or ATPG-based techniques do not provide sufficient solutions for many verification instances. Boolean function hashing is a probabilistic verification approach which can complement existing formal methods in a number of applications such as equivalence checking, biased random simulation, power analysis and power optimization. The proposed hashing technique is based on the arithmetic transform, which maps a Boolean function onto a probabilistic hash value for a given input assignment. The presented algorithm uses multiple-vertex dominators in circuit graphs to progressively simplify intermediate hashing steps. The experimental results on benchmark circuits demonstrate the robustness of our approach.


PURPOSE
To determine to what extent the benefits of cisplatin-based combination chemotherapy have been disseminated to all American men diagnosed with advanced testicular cancer.

PATIENTS AND METHODS
One hundred seventy-two advanced testicular cancer cases from five population-based registries of the Surveillance, Epidemiology, and End Results (SEER) Program diagnosed from 1978 to 1984 were compared with 133 diagnostically comparable cases from the Memorial Sloan-Kettering Cancer Center (MSKCC) vinblastine, dactinomycin, and bleomycin (VAB) regimens 7 through 9. Exclusions were made in both series for cases with elevated markers only, abdominal disease only, or extragonadal tumors. Ratings of extent of disease using the Indiana University system (minimal/moderate or advanced) were available for the MSKCC cases, and were determined retrospectively on the SEER cases based on information abstracted from medical records.

RESULTS
Among the SEER cases, 89% reported receiving chemotherapy, and 95% of these received cisplatin-containing regimens. Survival among the MSKCC patients was significantly better than for the SEER cases in the minimal/moderate extent of disease category (95% and 73% 3-year survival rate, respectively); however, the difference for advanced cases was only marginally significant (52% and 40% 3-year survival rates, respectively). Survival did not vary significantly by year of diagnosis in either series.

CONCLUSION
Although most of the patients in the SEER series received cisplatin-based chemotherapy, this alone did not produce results equivalent to that in the MSKCC series. Since the patients were selected to be as diagnostically comparable as possible at baseline, remaining differences in survival may be due to adherence to a fixed regimen and level of dose-intensity, adequacy of diagnostic work-up, implementation of salvage therapies and debulking surgery, and unknown factors related to who is willing and able to travel to a tertiary care center for treatment. Whatever the reason for not achieving optimal results in the SEER series, the very modest survival improvements over the time period 1978 to 1984 indicates that the differences in outcome between the two series were basically stable over the study period.


Hydroxyapatite (HAp), the main mineral content of bones and teeth, is one of the most important calcium phosphate-based bio-ceramics. Due to its crystal structure, it has the potential to be used as a low cost and biocompatible adsorbent. In this study, nano-synthesized and well-crystallized HAp was used in adsorption process of copper which causes growth problems. In order to investigate the synthesized nano-HAp crystal structure and functional groups, x-ray diffraction pattern (XRD), Fourier transform infrared (FTIR) spectroscopy and transmission electron microscopy analyzes were performed. Nano-HAp concentration, copper concentration and time were selected as variables affecting copper adsorption and Box-Behnken design was applied. According to the results, it was found that at least 33 min and 510 mg l−1 nano-HAp concentration was required to achieve a higher removal rate than 90% removal efficiency. It was determined that all selected independent variables are effective in copper removal. The optimization study was carried out with the findings obtained from the study and 514.0 mg l−1 nano-HAp and 60.4 min were found to be required for optimal removal. Moreover, the lowest selected Cu concentration can be totally removed by 700 mg l−1 nano-HAp and in 60.4 min of reaction time. This study demonstrates that nano-HAp can be used as an environmentally friendly adsorbent for copper removal from aqueous solution.


1. Involving communities in sustainable wildlife management in tropical forests can ensure food security and livelihoods of millions of forest dwellers that depend on wild meat, but also safeguard hunted species. Mathematical models have been developed to assess hunting sustainability; but these require empirical information on reproductive parameters of the prey species, often challenging to obtain. 2. Here, we suggest that if local people can accurately identify the reproductive status of hunted animals in the field, these data could fill the existing knowledge gap regarding species' life-history traits and enable better assessments of hunting impacts. 3. We first tested whether local people in 15 rural communities in three Amazonian sites could accurately diagnose, before and after training, the pregnancy status of hunted pacas (Cuniculus paca), which we use as our model. We then applied the results from these tests to correct reproductive status data of hunted specimens, voluntarily collected over 17 years (2002-2018) as part of a citizen science project in one of our study sites. We ran generalized additive models to contrast these corrected reproductive rates with those obtained from the direct analysis of genitalia by researchers, and with indices describing game extraction levels (catch-per-unit-effort, CPUE, and age structure of hunted individuals). 4. Before training, interviewees correctly diagnosed pregnancy in 72.5% of tests, but after training, interviewees accurately diagnosed pregnancy in 88.2% of tests, with high improvements especially for earlier pregnancy stages. Monthly pregnancy rates determined by hunters and by researchers were similar. Reported annual pregnancy Page 3 of 45 Confidential Review copy Journal of Applied Ecology 4 rates were negatively correlated with CPUE, and positively correlated with the percentage of immatures in the hunted population, in accordance to an expected densitydependent response to variations in hunting levels. 5. We showed that the voluntary diagnosis of game species' reproductive status by local people is a feasible method to obtain accurate life-history parameters for hunted tropical species, and to assess hunting effects on game populations. Given that almost half of the protected areas in the world are co-managed by local people, our results confirm the potential of integrating local communities in citizen science initiatives to ensure faster, low-cost, and more accurate data collection for wildlife management.


Increasing the porosity of oxycarbosilane dielectrics is a key approach to lower the interconnect signal delay and thus enable manufacturing of lower power consumption and higher performance microprocessors. However, this path leads to excessive dielectric process damage as the industry adapts procedures developed for dense and microporous insulators to mesoporous materials. Currently ultralow dielectric constant (k) materials cannot be integrated at the most aggressive pitch. Here, it is reported that the post porosity plasma protection enables the mitigation of process damage across a wide range of porosity regimes. The exponential increase in plasma damage with porosity when going from microporous k = 2.4 to mesoporous k = 1.8 is shown. Using the same range of materials, the strategy allows a reduction in process damage to a constant minimal level on both blanket wafers and patterned structures. The results demonstrate how the strategy can enable the extendibility of current materials and processes to future technology nodes.


Abstract We examine managers'' disclosure decisions in response to non-fundamental price shocks. Using mutual fund fire sales as a source of market disruption, we show some firms respond by issuing earnings guidance. Others, especially firms with weaker performance and more short-term-oriented investors, engage in accrual-based earnings management. To identify the efficacy of firm disclosure choices, we examine passage of Sarbanes-Oxley and Regulation Fair Disclosure and show that they increased reliance on guidance rather than earnings management. The shift is associated with faster post-fire-sales price recovery, suggesting enhancing information disclosure rather than manipulation is effective in mitigating the effect of market disruptions.


This collection combines humour and mystery to present a view of contemporary urban life. It features photographs from many cities including London, New York, Paris, Rome, Auckland and Sydney. Directed by signs, lights, warnings, we are encouraged to conform. But there are signs of dissent - small anarchies for the observant - unexpected intrusions by the untamed world into this controlled and controlling environment. The author sets out to illuminate these intrusions and offer up their mystery and their intrigue. He also maps the ambiguities and tensions in the urban environment of the late 20th-century.


[1] Ozone (O3) and aerosol scattering ratio profiles were obtained from airborne lidar measurements on thirty-eight flights over seven deployments covering the latitudes of 40°–85°N between 4 February and 23 May 2000 as part of the Tropospheric Ozone Production about the Spring Equinox (TOPSE) field experiment. Each deployment started from Broomfield, Colorado, with bases in Churchill, Canada, and on most deployments, Thule Air Base, Greenland. Nadir and zenith lidar O3 measurements were combined with in situ O3 measurements to produce vertically continuous O3 profiles from near the surface to above the tropopause. Potential vorticity (PV) distributions along the flight track were obtained from several different meteorological analyses. Ozone, aerosol, and PV distributions were used together to identify the presence of pollution plumes and stratospheric intrusions. Ozone was found to increase in the middle free troposphere (4–6 km) at high latitudes (60°–85°N) by an average of 4.6 ppbv/mo (parts per billion by volume per month) from about 54 ppbv in early February to over 72 ppbv in mid-May. The average aerosol scattering ratios at 1064 nm in the same region increased rapidly at an average rate of 0.36/mo from about 0.38 to over 1.7. Ozone and aerosol scattering were highly correlated over the entire field experiment, and PV and beryllium (7Be) showed no significant positive trend over the same period. The primary cause of the observed O3 increase in the mid troposphere at high latitudes was determined to be the photochemical production of O3 in pollution plumes with less than 20% of the increase from stratospherically-derived O3.


PURPOSE
This study aimed to determine the association between functional impairment in small airways and symptoms of dyspnea in patients with Long-coronavirus disease (COVID), using imaging and computational modeling analysis.

PATIENTS AND METHODS
Thirty-four patients with Long-COVID underwent thoracic computed tomography and hyperpolarized Xenon-129 magnetic resonance imaging (HP Xe MRI) scans. Twenty-two answered dyspnea-12 questionnaires. We used a computed tomography-based full-scale airway network (FAN) flow model to simulate pulmonary ventilation. The ventilation distribution projected on a coronal plane and the percentage lobar ventilation modeled in the FAN model were compared with the HP Xe MRI data. To assess the ventilation heterogeneity in small airways, we calculated the fractal dimensions of the impaired ventilation regions in the HP Xe MRI and FAN models.

RESULTS
The ventilation distribution projected on a coronal plane showed an excellent resemblance between HP Xe MRI scans and FAN models (structure similarity index: 0.87 ± 0.04). In both the image and the model, the existence of large clustered ventilation defects was not identifiable regardless of dyspnea severity. The percentage lobar ventilation of the HP Xe MRI and FAN model showed a strong correlation (ρ = 0.63, P < 0.001). The difference in the fractal dimension of impaired ventilation zones between the low and high dyspnea-12 score groups was significant (HP Xe MRI: 1.97 [1.89 to 2.04] and 2.08 [2.06 to 2.14], P = 0.005; FAN: 2.60 [2.59 to 2.64] and 2.64 [2.63 to 2.65], P = 0.056).

CONCLUSIONS
This study has identified a potential association of small airway functional impairment with breathlessness in Long-COVID, using fractal analysis of HP Xe MRI scans and FAN models.


The Hf isotope composition of rutile in mica-amphibole-rutile-ilmenite-diopside (MARID) xenoliths from the Kimberley area of South Africa has been analyzed in situ by laser ablation microprobe–multicollector–inductively coupled plasma mass spectrometry to investigate metasomatic processes in the lithospheric mantle. The 176Hf/177Hf ratio shows a wide range, from 0.2811 to 0.2858 (eHf = −55 to +110); much of this range is found within single samples and even within single grains. We suggest that the MARID rutiles initially resulted from the interaction of an asthenospheric melt with ancient depleted harzburgitic mantle with low 176Hf/177Hf ratios (<0.2812) and Lu/Hf ratios of ∼0.04, that dominated their Hf budget. The MARID rocks were later metasomatized by a fluid and/or melt that had caused the breakdown of eclogitic or lherzolitic garnet with Lu/Hf ratios of ∼0.6, providing a source of highly radiogenic Hf. The low 176Hf/177Hf ratios preserved in some MARID rutiles show that the Nd-Hf isotope systematics of kimberlites and lamproites can be explained by mixing between an asthenospheric melt and the ancient subcontinental lithospheric mantle.


Nine cases of acquired absence of the fibular shaft were studied to determine the growth contribution of the distal fibula; in 6 cases the absence was caused by osteomyelitis and in 3 cases by trauma. The average valgus and external rotational deformities were 15.2 degrees and 10 degrees, respectively. In 3 of 7 cases surgically treated with Langenskiöld operation or supramalleolar corrective osteotomy, the valgus deformity recurred during the postoperative growth period. The speculated causes of gradual valgus deformity are the loss of physiologic thrust from the proximal to distal fibula, the tethering effect of contracted soft tissue on distal fibula and early physeal closure of the lateral part of the distal tibia due to continuous, uneven axial overloading. The Langenskiöld operation was found effective for the stability of ankle joint in the initial period, but could not prevent the postoperative revascularization of the ankle. However, it is strongly recommended that any types of prophylactic surgery should be carried out before the development of an epiphyseal deformity of distal tibia, and to prevent secondary osteoarthritis of the ankle joint.


Recent evidence shows the involvement of reactive oxygen species (ROS) in the mitogenic cascade initiated by the tyrosine kinase receptors of several growth factor peptides. We have asked whether also the vascular endothelial growth factor (VEGF) utilizes ROS as messenger intermediates downstream of the VEGF receptor-2 (VEGFR-2)/KDR receptor given that the proliferation of endothelial cells during neoangiogenesis is physiologically regulated by oxygen and likely by its derivative species. In porcine aortic endothelial cells stably expressing human KDR, receptor activation by VEGF is followed by a rapid increase in the intracellular generation of hydrogen peroxide as revealed by the peroxide-sensitive probe dichlorofluorescein diacetate. Genetic and pharmacological studies suggest that such oxidant burst requires as upstream events the activation of phosphatidylinositol 3-kinase and the small GTPase Rac-1 and is likely initiated by lipoxygenases. Interestingly, ROS generation in response to VEGF is not blocked but rather potentiated by endothelial nitric-oxide synthase inhibitors diphenyleneiodonium and N Gmethyl-l-arginine, ruling out the possibility of nitric oxide being the oxidant species here detected in VEGF-stimulated cells. Inhibition of KDR-dependent generation of ROS attenuates early signaling events including receptor autophosphorylation and binding to a phospholipase C-γ-glutathione S-transferase fusion protein. Moreover, catalase, the lipoxygenase inhibitor nordihydroguaiaretic acid, the synthetic ROS scavenger EUK-134, and phosphatidylinositol 3-kinase inhibitor wortmannin all reduce ERK phosphorylation in response to VEGF, and antioxidants prevent VEGF-dependent mitogenesis. Finally, cell culture and stimulation in a nearly anoxic environment mimic the effect of ROS scavenger on receptor and ERK phosphorylation, reinforcing the idea that ROS are necessary components of the mitogenic signaling cascade initiated by KDR. These data identify ROS as a new class of intracellular angiogenic mediators and may represent a potential premise for new antioxidant-based antiangiogenic therapies.


Various efforts have been undertaken by universities to improve academic quality control.
This effort is intended to improve the quality of education. Evaluation of the monitoring
process is carried out continuously and continuous in the end will be able to fix the quality of
education. One of the efforts is to build information systems design exam. With the
availability of information systems exam is expected that users can perform a variety of
analysis and also can provide a more accurate exam. Development of information system
design is intended as a first step in increasing the academic quality of universities.


Minami, M., Okada, A., Takizawa, A., and Kubota, J. (1972).Brit. J. industr. Med.,29, 321-327. Effect of ethylene glycol dinitrate on metabolism of catecholamines and on blood pressure reaction to re-exposure. Male Donryu rats were divided into two groups. One group was given 65 mg/kg per day of ethylene glycol dinitrate (EGDN) subcutaneously for five days and the other group received the same for 10 days. On the first, second, third, fourth, and fifth days after the last injection of EGDN catecholamines were estimated in the heart, brain, and adrenals and plasma 11-hydroxycorticosteroids and haemoglobin were estimated in blood. Urine samples were collected for 24 hours every other day before, during, and after the period of EGDN injection. After five successive doses of EGDN the concentration of catecholamines in the organs increased and urinary catecholamine excretion was a little greater than from the controls. Reinjection of EGDN caused prolonged irreversible depression of the blood pressure. After 10 successive doses of EGDN the concentrations of catecholamines in the organs were normal, but noradrenaline excretion in the urine was increased for three days. Reinjection of EGDN on the first day caused prolonged depression of blood pressure, but by five days the response had returned to the more transient depression observed in the controls. The probability of coronary spasm is considered to be greater in the condition found after five than in that after 10 successive injections because more noradrenaline was available in the cardiac muscle as well as adrenaline in the adrenals. After 10 successive injections the increased noradrenaline concentration in the urine reflected the raised noradrenaline level in the blood which could alleviate the depressant action of EGDN reinjection. The clinical significance of these findings is discussed.


This report deals with paca sleeping dens (Cuniculus paca Linnaeus, 1766). The study was conducted between August 2006 and April 2007 and is based on detailed observations. Results indicate that this rodent uses holes in the ground or in fallen trees as sleeping dens. Each of these sleeping dens had two or more orifices and an internal cavity for the "diurnal sleep". Typically, one orifice was for common use and the rest for the circumstantial escape. According to their form, their localization in the ground, and the number and location of orifices, sleeping dens were classified into four types, of which type A was the most common. The results also indicate a greater concentration of sleeping dens in temporary flooded gallery forest.


We study the Combinatorial Thompson Sampling policy (CTS) for combinatorial multi-armed bandit problems (CMAB), within an approximation regret setting. Although CTS has attracted a lot of interest, it has a drawback that other usual CMAB policies do not have when considering non-exact oracles: for some oracles, CTS has a poor approximation regret (scaling linearly with the time horizon $T$) [Wang and Chen, 2018]. A study is then necessary to discriminate the oracles on which CTS could learn. This study was started by Kong et al. [2021]: they gave the first approximation regret analysis of CTS for the greedy oracle, obtaining an upper bound of order $\mathcal{O}(\log(T)/\Delta^2)$, where $\Delta$ is some minimal reward gap. In this paper, our objective is to push this study further than the simple case of the greedy oracle. We provide the first $\mathcal{O}(\log(T)/\Delta)$ approximation regret upper bound for CTS, obtained under a specific condition on the approximation oracle, allowing a reduction to the exact oracle analysis. We thus term this condition REDUCE2EXACT, and observe that it is satisfied in many concrete examples. Moreover, it can be extended to the probabilistically triggered arms setting, thus capturing even more problems, such as online influence maximization.


BACKGROUND
ACE polymorphism, especially genotype DD or D allele, may be involved in the progression of diabetic nephropathy. It may also have different effects on the reduction of proteinuria by ACE inhibitors in patients with proteinuria. We investigated the relationship between ACE gene polymorphism and antiproteinuric effect of ACE inhibitors (Benazepril 10 mg/day or Perindopril 4 mg/day) in 83 NIDDM patients with overt proteinuria (urinary protein excretion over 500 mg/day).

METHODS
We recruited NIDDM patients with overt proteinuria from our renal clinic. Before entry, previously used ACE inhibitors were withdrawn for at least 2 weeks and baseline proteinuria and albuminuria were measured. Patients were classified into three groups in accordance with ACE genotypes (17 DD; 33 ID; 33 II) and prospectively followed up for 3 months. Various clinical parameters including age, DM duration, body mass index (BMI), 24-h urine sodium, protein and albumin, BUN, serum creatinine, creatinine clearance (Ccr), mean arterial pressure (MAP), and HbA(1c) were measured in the pre- and post-treatment periods. ACE genotypes were determined by polymerase chain reaction.

RESULTS
There were no significant differences in the clinical parameters such as age, DM duration, BMI, BUN, serum creatinine, Ccr, MAP, HbA(1c), and daily urinary excretion of sodium, protein and albumin among three groups (P>0.05). After the 3-month treatment period using ACE inhibitors, there were no significant differences in the reduction of MAP and Ccr among the three groups (P>0.05). However, the percentage reductions in urinary excretion of protein and albumin for DD genotype were significantly higher than in ID and II genotypes (50.9+/-19.2% vs 19.2+/-16.0%, 20.2+/-20.4%; 52.6+/-23.6% vs. 13.5+/-51.8%, 24.8+/-23.9%, P<0.05). There were no statistically significant correlations between the levels of baseline proteinuria and albuminuria and the magnitudes of the reduction of proteinuria and albuminuria under ACE inhibition (P>0.05).

CONCLUSIONS
Our results suggest that the ACE gene polymorphism might have a role in determining the responsiveness to the antiproteinuric effect of ACE inhibition in proteinuric NIDDM patients.


INTRODUCTION AND OBJECTIVES: Renal artery aneurysms represent a rare clinical entity, and most are managed with endovascular techniques when treatment is indicated. Laparoscopic and robot assisted repair of renal artery aneurysms has been described; however, few reports exist in the literature. The aim of this video is to describe a robot assisted laparoscopic technique for resection and repair of a renal artery aneurism when endovascular treatment is not amenable. METHODS: We present the clinical case of a 32 year-old woman, smoker, with desire for pregnancy and a right renal aneurysm of 21x17 mm that was found in a CT scan performed due to a thoracic trauma in February 2017. The CT angiogram showed 4 vessels of the same calibre arising from the aneurysm and going to the parenquima. The placement of a multilayer stent was ruled out due to the complexity of the aneurysm and the patient was proposed a robot assisted laparoscopic repair. The technique used is explained in the video. RESULTS: Serum creatinine levels 24 hours after surgery were 53 umol/L. The angiogram 24 hours after surgery showed an homogeneous arrival of the tracer in all the parenquima without ischemic zones. The patient was discharged 72 hours after the surgery without complications. The ultrasound 1 week after surgery had no significant findings and the vascular parameters of the kidney were normal. CT angiogram 1 month later showed the whole kidney well perfused and the aneurysm repaired respecting the 4 branches. CONCLUSIONS: Robot-assisted laparoscopic renal artery aneurysm repair is an option when endovascular treatment is not amenable. The use of the robotic surgical platform facilitated aneurysm resection and suturing during this procedure, avoiding extracorporeal repairing surgery and autotransplantation. Source of Funding: None


Torsional dynamic analysis of carbon nanotubes under the effect of longitudinal magnetic field is carried out in the present study. Torque effect of an axial magnetic field on a carbon nanotube has been defined using Maxwell's relation. Nonlocal governing equation and boundary conditions for carbon nanotubes are obtained by using Hamilton's minimum energy principle. Eringen's nonlocal stress gradient elasticity theory is used in the formulation. Fourth order nonlocal equation of motion is solved by utilizing differential quadrature method. Clamped-clamped and clamped-free nonlocal boundary conditions are considered. Nonlocal and axial magnetic field effects on torsional vibration of carbon nanotubes are investigated. The magnetic field has significant effects on the dynamics of carbon nanotubes and may lead to torsional buckling. Critical torsional buckling load reduces with nonlocal effects. Nonlocality shows softening effect on carbon nanotube's lattice structure. Present results can be used in the design and analysis of nanoelectromechanical products like nano-motors.


In a greenhouse study conducted in 1999 and 2000 with soils from the Institute of Agricultural Research Experimental Farms, Samaru, (Latitude 11°11'N and Longitude 7°38'E) in the northern guinea savanna (NGS) agro-ecological zone of Nigeria, the effects of different levels of foliar fertilizer (Algifol) and in a combination of granular NPK fertilizers on tomato cultivar, Roma-VF, were determined. Observations were made on plant height, number of leaves and fresh fruits yield per plant. The results showed that treatments effect on plant height at 6 and 10 weeks after transplant (WAT) were not significant (P=0.05) in 1999 but was highly (P=0.01) significant at 10WAT in 2000. Leaves per plant were not significantly (P=0.05) different against treatments at 6WAT in both years but at 10WAT, the effect was highly significant (P=0.01). Fresh fruits yield/plant in 1999 was significant (P=0.05) and highly significant (P=0.01) in 2000. Combined application ranked best in growth and yield of tomato than with either single Algifol or NPK in view of its greater nutrient resources to meet crop needs. Keywords : foliar, savanna, conventional NPK, Algifol, combined application. Global Journal of Agricultural Sciences Vol. 4(2) 2005: 129-133


Reserves Estimation obtained through calculation and analysis of exploration data
that have been obtained in the form of data drilling, strike, dip, and thickness of coal.
Reserves Assessment conducted in order to determine the estimated amount of tonnage of
coal reserves. Locations mapping located in the concession area of PT Primary Minerals
Tabalong covering 128.9 hectares, located in Paju District Epat, East Barito regency, Central
Kalimantan province.
The purpose of this study was to apply the method of Cross Section in determining
the amount of coal reserves and coal resource estimate number of research areas
The method used in this study is by observation in the field, while the method of
valuation reserves Cross Section used method by comparing the incremental changes to the
guidelines guidelines nearest point
The results are expected to determine the volume of resources in the overburden,
Seam A and Seam B, determine the tonnage of coal, and the stripping ratio (SR).The
conclusion by using the method of Cross Section with gradual changes guidelines (rule of
gradual change), the distance between the incision of 33-394 meters and obtained Reserves
Measured (Measured Reserve) was 1,063,082.35 tons Seam A and Seam B is 786 476 , 44
tons, so the total coal tonnage was 1,849,559.04 tons. Obtained overburden volume
amounted to 16,121,507 BCM, SR 8,72:1.
Methods Cross Section with guidance closest point (rule of nearest point) to the
distance between the incision of 16.5 to 309 meters and earned Measured coal reserves
(Measured Resource) is 1,080,008.8 tons Seam A and Seam B is 28788.344,05 ton , so the
total tonnage of coal was 1,868,352,85 tons. and overburden volume amounted to
316,293,970 BCM, SR 8,72:1.


The Avocado Growers Association on the island of Hawaii requested that the USDA-APHIS reconsider the possibility of approving the export of untreated avocado to the continental USA. In response, as part of the Hawaii Area Wide Pest Management Program, the Agricultural Research Service undertook a survey to supplement the original survey conducted by Liquido et al. (1995). This consisted of deploying traps baited with male lures for the three invasive species (Bactrocera dorsalis (Hendel), B. cucurbitae (Coquillett), and Ceratitis capitata (Wiedemann)) and protein bait traps for general detection of females within orchards. The survey was concentrated in the Kona District, and the orchards were mapped using a geographic information systems approach. In addition, between 9 August 2006 until 22 May 2007, 519 avocado fruits were collected from the ground and held individually to determine the presence of fruit fly larvae. Because male lure trap captures varied with locality and season and attracted flies from large distances, they are probably of limited value in predicting numbers of fruit flies within small avocado orchards. On the other hand protein bait traps, because they captured females and attracted flies from short distances, were a better indication of female flies found within orchards. C. capitata was the most prevalent species year round (0.456 ± 0.130 ♀ flies/trap/day). B. dorsalis was captured considerably less frequently (0.096 ± 0.068 ♀ flies/trap/day). B. cucurbitae was the least prevalent species in avocado orchards, averaging 0.034 ± 0.006 ♀ flies/trap/day. Adult fly emergence from the ground fruit sample was 1.25 x 10 -05 ± 8.89 x 10 -6 B. dorsalis flies/g of fruit and no C. capitata emerged from any fruit sample. That is a fruit infestation rate of 0.385% and a rate of 0.771% larvae per fruit. All of the fruits sampled had some damage that would have excluded them from shipment by previous export criteria.


Purpose: Purpose of this study is study of Students attitude and dispelling of its related barriers at educational environments by educational decision makers.
Design: This is a descriptive- analytical study.
Subjects: Sampling did randomly and during the evaluation external evaluation team headquarters of the ministry of health and from general medicine clinical students (level interns and externs) during the 2008 to 2013. The number of universities under study has been 102. The total sample size was 2,810 students. In order to reduce the errors and increasing the accuracy, students in basic science and physiopathology levels, were excluded from the study.
Measures: it this study it has been tried that governing space on the educational environment tested by DREEM (The Dundee Ready Educational Environment Measure).
Results: The results show that university students attitude under study during the years of 2008 until 2013 on average were 109 of the 200 scores. Results show in 2008 score of 134, in 2009 score of 99, in 2010 score of 101, in 2011 score of 106, in 2012 score of 107 and in 2013 score of 108. Mean of earned total score during these years is 109 score.
Conclusion: This information show significant differences up to score of 200 standard questionnaires. Groups of 3 included scores of 101-150, that show more positive students concept of attitude than negative.


This paper compares the educational thoughts of Obafemi Awolowo and Tai Solarin. Its methodology is critical and comparative. The paper argues that the variations of the political
philosophies of the two thinkers account for the differences in their views on education. It further contends that the educational ideas of both thinkers reflect African cultural experiences. The paper also explores the possibility of integrating the insights of the two thinkers into the educational policies and practices of contemporary African societies.


Three types of TiAl-Nb ternary alloys are obtained by arc-melting and heat treatment, which are γ-TiAl single phase, γ-TiAl + α2-Ti3Al duplex phase and γ-TiAl +α2-Ti3Al +Nb2Al multiple phase alloy. The phase stability is studied using X-ray diffractometer and electron probe microanalyzer. Mechanical properties are investigated through compress and tensile tests at RT to 1373K. It is found that, their mechanical properties are related to their microstructures. The deformability of alloy B is better than that of alloy A and C at RT due to small grain size reduced by α2 phase appearance, lamellar microstructure and interfaces. The deformability of alloy B increases significantly with increasing temperature, the elongation of alloy B achieves 40.4% at 1173K. The fracture mode of alloy B changed from brittle transgranular failure at room temperature to ductile intergranular failure at 1173K. While, both of alloy A and C have not increased its deformability at 1173K and showed brittle transgranular failure at both temperatures. Alloy C was a very brittle material at room and high temperature due to Nb2Al phase appearance, which reducing the continuity of (γ+α2) lamellar structure.


In this paper, we proposed to improve performance of the design of a cascade controller with the smith-predictor structure. The parameters of controller in the inner loop are determined to minimize the integral of time multiplied by the absolute value of error (ITAE) value of performance Index. The controller of outer loop and parameters of Smith-Predictor can be obtain using reduction model. The model reduction is considered that it is the transient response and the steady-state response through the use of nyquist curve. Simulation examples are given to show the better performance of the proposed method than conventional methods.


Previous studies have shown that Wnt3a enhances the proliferation and inhibits the osteogenic differentiation of human mesenchymal stem cells (hMSCs). In this study, we investigated the signaling pathways involved in Wnt3a‐induced osteoblastic cell proliferation. Experiments with DKK1, a natural antagonist of Lrp5/6, indicated that Wnt/β‐catenin did not play a major role in Wnt3a‐induced osteoblastic cell proliferation. The use of selective inhibitors of known mitogenic pathways implicates Src family kinases (SFKs) and a protein kinase C (PKC) in this cellular response. Time‐dependent analysis of signaling molecules activated by Wnt3a in MC3T3‐E1 cells revealed parallel activation of the canonical pathway and of several tyrosine kinases, including SFKs and PDGF receptors (PDGF‐Rs). Functional analysis with specific inhibitors suggested a major role of PDGF‐Rs in mediating Wnt3a‐induced cell proliferation. Further investigation with an si‐RNA approach confirmed a predominant role of this receptor in this cellular response. The use of soluble decoy PDGF‐Rs that can sequester extracellular PDGFs excluding that part of the increased PDGF receptor phosphorylation by Wnt3a was the result of autocrine production of PDGFs. A selective SFK inhibitor blunted the enhanced PDGF‐R phosphorylation and cell proliferation induced by Wnt3a. Studies of initial events involved in the regulation of this pathway suggest a role of dishevelled. In conclusion, data presented in this study indicate that cell proliferation induced by Wnt3a in osteoblastic cells is mediated by a dishevelled‐dependent and β‐catenin‐independent pathway, which involves the transactivation of PDGF receptors. © 2013 American Society for Bone and Mineral Research


Abstract:  Two new nematode species are described from the paddlefish Polyodon spathula (Walbaum) (Polyodontidae, Acipenseriformes) from the Mississippi River drainage, United States, based on specimens previously deposited in the U.S. National Parasite Collection. Those specimens were Camallanus polyodontis n. sp. (Camallanidae) from the host (site of infection not given) collected in the Yellowstone River, Montana in 1974 and Syngnathinema chitwoodi n. sp. (Daniconematidae) from the body cavity of fish collected in Mississippi in 1926. Camallanus polyodontis (male and female) is mainly characterized by the presence of a conspicuously large, oval, sclerotized formation at the base of tridents on the buccal capsule, by which it distinctly differs from all congeners. It also differs from other North American species of the genus by additional features such as the body size, the length of spicules, or the length of the female tail. Syngnathinema chitwoodi (a single subgravid female) differs from the only other congener, Syngnathinema californiense Moravec, Spangenberg and Frasca, 2001, a parasite of the circulatory system of the pipefish in California and British Columbia, mainly in that the posterior end of the muscular esophagus is not submerged into the anterior end of the glandular esophagus. Previous reports of Camallanus oxycephalus Ward and Magath, 1917 in P. spathula may be misidentifications of C. polyodontis.


1. Stretches of regenerating rabbit's nerve in which no connexion with the periphery is allowed contain numerous and small nerve fibres.

2. Both cutaneous sensory and motor nerve fibres become large when allowed to reach their endorgans, but the motor fibres attain greater diameters than the cutaneous sensory fibres.

3. Motor fibres regenerating without opportunity of reaching muscle fibres become little if any larger than sensory fibres when both are unable to reach their end-organs. It is, therefore, probable that the peripheral connexion is of great importance in determining fibre diameter.

4. The fibres of the central stump of a nerve regenerating unconnected with the periphery remain small and have relatively very thick myelin sheaths.

5. The diameter of nerve fibres regenerated in the region below a crushed point on a nerve is not influenced by the length of nerve to be regenerated distally.

6. Increase of diameter and medullation proceeds centrifugally from a lesion, more distant points showing a lesser degree of maturation at any given time.

7. Fibres regenerated in a grafted piece of posterior tibial nerve were only slightly smaller than those in a grafted piece of peroneal nerve. Connexion with the periphery is, therefore, able to produce an increase in fibre diameter which over-rides any constriction of fibre growth produced by the slightly smaller Schwann tubes.

Leverhulme Research Scholar, Royal College of Surgeons of England.


Summary
It is suggested that the infarcts occurring in the spleen in malaria may result from an obstruction produced by hyperplasia of the reticular-like cells located within the walls of the venous sinuses. Leucocytes and red blood cells may adhere to the surface of these masses of reticular-like cells since the circulation in malaria is slowed. The normal histological structures in the spleen of different animals are discussed that may predispose to vascular obstruction.


Peroxisome proliferator-activated receptor γ (PPARγ) and transforming growth factor-β (TGF-β) are key regulators of epithelial cell biology. However, the molecular mechanisms by which either pathway induces growth inhibition and differentiation are incompletely understood. We have identified transforming growth factor-simulated clone-22 (TSC-22) as a target gene of both pathways in intestinal epithelial cells. TSC-22 is member of a family of leucine zipper containing transcription factors with repressor activity. Although little is known regarding its function in mammals, theDrosophila homolog of TSC-22,bunched, plays an essential role in fly development. The ability of PPARγ to induce TSC-22 was not dependent on an intact TGF-β1 signaling pathway and was specific for the γ isoform. Localization studies revealed that TSC-22 mRNA is enriched in the postmitotic epithelial compartment of the normal human colon. Cells transfected with wild-type TSC-22 exhibited reduced growth rates and increased levels of p21 compared with vector-transfected cells. Furthermore, transfection with a dominant negative TSC-22 in which both repressor domains were deleted was able to reverse the p21 induction and growth inhibition caused by activation of either the PPARγ or TGF-β pathways. These results place TSC-22 as an important downstream component of PPARγ and TGF-β signaling during intestinal epithelial cell differentiation.


This paper considers semi-supervised learning for tabular data. It is widely known that Xgboost based on tree model works well on the heterogeneous features while transductive support vector machine can exploit the low density separation assumption. However, little work has been done to combine them together for the end-to-end semi-supervised learning. In this paper, we find these two methods have complementary properties and larger diversity, which motivates us to propose a new semi-supervised learning method that is able to adaptively combine the strengths of Xgboost and transductive support vector machine. Instead of the majority vote rule, an optimization problem in terms of ensemble weight is established, which helps to obtain more accurate pseudo labels for unlabeled data. The experimental results on the UCI data sets and real commercial data set demonstrate the superior classification performance of our method over the five state-of-the-art algorithms improving test accuracy by about $3\%-4\%$. The partial code can be found at this https URL.


The typical engineering homework assignment may involve sketches, formulas with special symbols, as well as calculation steps. The most time efficient way for students to do this work is by hand, on paper. In terms of grading such assignments, it is faster and easier for instructors to handwrite comments than to add typewritten comments via text box, sticky note, etc. The computer and printing technologies available to instructors and students have progressed to the point where the use of electronic submission and grading for assigned work is viable, both in terms of ease of use and the benefits accrued – even for handwritten assignments. The goal for this project is to implement and assess a "paperless grading" process for handwritten homework assignments which allows for both electronic submission and return of the assignments. This process also allows the grader to "mark-up" the papers with handwritten comments. In spring 2013, the 33 students in the "Engineering Systems" class participated in a semester long trial of a paperless grading process for their homework assignments. An iPad was used as the homework grading platform coupled with the university's course management system. At the end of the semester, the students completed a survey with questions which asked them to compare the paperless process with the process associated with the more traditional homework submission and grading process as well as their opinions on possible benefits or disadvantages of the paperless process. Also included were questions asking for their suggestions for improvements on the paperless process. Student feedback from this first trial was used to make some enhancements to the paperless process which was repeated in the spring 2014 offering of the class with 60 students who then completed the same survey used in 2013. This study shows that the penultimate "hold out" of going paperless – handwritten homework – can be accomplished with the hybrid process to be described in this paper. All participants in both semesters – students, graders, and instructor – concur that paperless grading is the way to go. In this paper, a more detailed description of the paperless grading process for handwritten homework will be presented. In addition, the quantitative results of the project evaluation for both semesters will be discussed as well as suggestions for future improvements in the process.


Pharmacy education has entered an era of focus on assessment of learning outcomes as an evidence-based approach to determine the effectiveness of instructional methods. Assessment of the learning outcomes is more important than the methods or the process of teaching. We know that what happens in the minds of our students is more important than what the instructor thinks about student learning. Journal authors now include much more information in their manuscripts to document student learning; nevertheless, many published reports in pharmacy education still do not provide adequate evidence of learning.

A scan of papers that have appeared in the Journal over the past few years shows many examples of measures that directly assessed student learning and others that focused on students' "perception" of their learning. While students' perceptions of their learning may provide a type of assessment, they should not be used as the primary evidence that an instructional approach is effective. Perception may not be reality.

When authors focus their assessment of learning on student perceptions, students are typically asked to rate on a survey instrument how well they believe they understood a topic, or how "confident" or "comfortable" they are regarding knowledge in an area. Student perceptions of their own knowledge may not accurately assess the higher-level knowledge they will need in practice. By the very act of participating in a course, students may perceive their learning has significantly improved. Instructor and student perceptions of learning are prone to multiple types of biases.

Instructors attempting to demonstrate the effectiveness of their instruction should not rely on student perceptions as the primary evidence of learning. Student perceptions of their learning may provide one subset of information but should not be the primary assessment. Often, student perception data are not validated as a measure of achievement of competencies. Evidence for learning and achievement of competencies should include direct measures of learning, which could be traditional examinations that address course competencies, structured instructor evaluations, use of assessment rubrics, or other direct assessments such as objective structured clinical evaluations (OSCEs). Guidelines for the assessment of learning are provided in the IDEAS paper by Poirier and colleagues.1 This document serves as a framework for an evidence-based approach to fully describe a new course or instructional approach. Other papers in the Journal provide additional guidance on assessment measures.2-5

Authors should note that manuscripts are unlikely to be published in AJPE if the only measure of learning is student perceptions of their own learning. Editors may return manuscripts to authors who only include student perception data, and manuscript reviewers are instructed to expect validated direct measures of student learning for articles that describe new instructional approaches.

The ultimate endpoint of interest to the pharmacy educator should be whether students achieve desired competencies that indicate the knowledge and skills that are needed to effectively practice pharmacy. Students' own perceptions of their knowledge and skills may not reflect reality or provide an accurate and thorough assessment, and should not serve as a primary measure of learning effectiveness. The quality of pharmacy education and education literature will be improved when standards for publication include the requirement for direct measures of student learning beyond student perceptions of their knowledge and skills.